Using the rat hypothalamo-neurohypophysial system as a model, we have isolated two large molecular weight common precursors (mol. wt. approximately 20,000) for vasopressin and its neurophysin (pro-pressophysin) and oxytocin and its neurophysin (pro-oxyphysin). Pro-pressophysin was shown to be glycosylated while pro-oxyphysin was not. A glycopeptide, presumably cleaved from pressophysin, since it is absent in rats with heredity diabetes insipidus, which do not synthesize vasopressin, has been isolated and its partial amino acid sequence determined. We have also demonstrated that the two prohormones are present in secretory granules, and their processing to the respective hormones can occur intragranularly.